EP0138765B1 - 4H-benzo[4,5]cyclohepta[1,2-b]thiophene derivatives - Google Patents
4H-benzo[4,5]cyclohepta[1,2-b]thiophene derivatives Download PDFInfo
- Publication number
- EP0138765B1 EP0138765B1 EP84810475A EP84810475A EP0138765B1 EP 0138765 B1 EP0138765 B1 EP 0138765B1 EP 84810475 A EP84810475 A EP 84810475A EP 84810475 A EP84810475 A EP 84810475A EP 0138765 B1 EP0138765 B1 EP 0138765B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- compound
- formula
- alkyl
- salt
- defined above
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- MHGBFEJHQLAUQM-UHFFFAOYSA-N 10h-benzo[1,2]cyclohepta[3,4-b]thiophene Chemical class C1=CC2=CC=CC=C2CC2=C1SC=C2 MHGBFEJHQLAUQM-UHFFFAOYSA-N 0.000 title description 2
- 150000002148 esters Chemical class 0.000 claims abstract description 30
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 77
- 238000000034 method Methods 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 27
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- -1 C1-4alkyl ester Chemical class 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 7
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical group NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims description 4
- XIKRQPKFOKKGGW-UHFFFAOYSA-N 2-(4-methoxybenzo[1,2]cyclohepta[3,4-b]thiophen-10-ylidene)acetic acid Chemical compound COC1=CC2=CC=CC=C2C(=CC(O)=O)C2=C1SC=C2 XIKRQPKFOKKGGW-UHFFFAOYSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- XIKRQPKFOKKGGW-LCYFTJDESA-N (2z)-2-(4-methoxybenzo[1,2]cyclohepta[3,4-b]thiophen-10-ylidene)acetic acid Chemical compound COC1=CC2=CC=CC=C2\C(=C\C(O)=O)C2=C1SC=C2 XIKRQPKFOKKGGW-LCYFTJDESA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- YZNKIGPMGBBSRI-UHFFFAOYSA-N 2-(4-hydroxybenzo[1,2]cyclohepta[3,4-b]thiophen-10-ylidene)acetic acid Chemical compound OC1=CC2=CC=CC=C2C(=CC(=O)O)C2=C1SC=C2 YZNKIGPMGBBSRI-UHFFFAOYSA-N 0.000 claims description 2
- 238000006052 Horner reaction Methods 0.000 claims description 2
- 238000005661 deetherification reaction Methods 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 claims 3
- 229960000583 acetic acid Drugs 0.000 claims 2
- 238000002360 preparation method Methods 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 8
- 230000001754 anti-pyretic effect Effects 0.000 abstract description 8
- 239000002221 antipyretic Substances 0.000 abstract description 5
- 230000000202 analgesic effect Effects 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 239000007858 starting material Substances 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 241000700159 Rattus Species 0.000 description 7
- 229940093499 ethyl acetate Drugs 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 206010003246 arthritis Diseases 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 206010037660 Pyrexia Diseases 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 229930194542 Keto Natural products 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000001760 anti-analgesic effect Effects 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002085 enols Chemical group 0.000 description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 3
- 125000000468 ketone group Chemical group 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 0 *OC(c1c2cc[s]1)=Cc(cccc1)c1C2=*C(O)=O Chemical compound *OC(c1c2cc[s]1)=Cc(cccc1)c1C2=*C(O)=O 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 208000009386 Experimental Arthritis Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 229940035423 ethyl ether Drugs 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- ZSGIVIUNURDDJL-UHFFFAOYSA-N 4-methoxybenzo[1,2]cyclohepta[3,4-b]thiophen-10-one Chemical compound COC1=CC2=CC=CC=C2C(=O)C2=C1SC=C2 ZSGIVIUNURDDJL-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 206010042618 Surgical procedure repeated Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 125000003500 enol ether group Chemical group 0.000 description 1
- PKGTYJFRXIVZFT-UHFFFAOYSA-N ethyl 2-(4-methoxybenzo[1,2]cyclohepta[3,4-b]thiophen-10-ylidene)acetate Chemical compound COC1=CC2=CC=CC=C2C(=CC(=O)OCC)C2=C1SC=C2 PKGTYJFRXIVZFT-UHFFFAOYSA-N 0.000 description 1
- ZCSPJXDUEHRREN-UHFFFAOYSA-N ethyl 2-(8-hydroxy-4-methoxybenzo[3,4]cyclohepta[1,3-b]thiophen-10-ylidene)acetate Chemical compound COC1=CC2=CC=C(O)C=C2C(=CC(=O)OCC)C2=C1SC=C2 ZCSPJXDUEHRREN-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000003108 foot joint Anatomy 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- MMEZQTJIISIGCZ-UHFFFAOYSA-N methyl 2-(4-methoxybenzo[1,2]cyclohepta[3,4-b]thiophen-10-ylidene)acetate Chemical compound COC1=CC2=CC=CC=C2C(=CC(=O)OC)C2=C1SC=C2 MMEZQTJIISIGCZ-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 208000030428 polyarticular arthritis Diseases 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
- C07D333/80—Seven-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- Increase in temperature for each rate is calculated and expressed as a % average increase determined in the control group (ca. 2.3°C above normal).
- the ED so estimated by regression analysis, is taken as the dosage at which increase in rectal temperature is 50% of that in the control group.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pain & Pain Management (AREA)
- Public Health (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Automotive Seat Belt Assembly (AREA)
- Indole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| MYPI87002008A MY102060A (en) | 1983-10-13 | 1987-09-28 | 4h-benzo(4,5)cyclohepta(1,2-b)thiophene derivatives |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB838327403A GB8327403D0 (en) | 1983-10-13 | 1983-10-13 | Organic compounds |
| GB8327403 | 1983-10-13 | ||
| GB8332660 | 1983-12-07 | ||
| GB838332660A GB8332660D0 (en) | 1983-12-07 | 1983-12-07 | Organic compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP0138765A2 EP0138765A2 (en) | 1985-04-24 |
| EP0138765A3 EP0138765A3 (en) | 1986-12-30 |
| EP0138765B1 true EP0138765B1 (en) | 1989-08-16 |
Family
ID=26286915
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP84810475A Expired EP0138765B1 (en) | 1983-10-13 | 1984-10-01 | 4H-benzo[4,5]cyclohepta[1,2-b]thiophene derivatives |
Country Status (18)
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8530245D0 (en) * | 1985-12-09 | 1986-01-22 | Sandoz Ltd | Organic compounds |
| HU203198B (en) * | 1987-10-26 | 1991-06-28 | Sandoz Ag | Process for producing pharmaceutical compositions having immunity-inhibiting, monokin-, particularly interleukin-1-inhibiting effect |
| GB9010332D0 (en) * | 1990-05-09 | 1990-06-27 | Sandoz Ltd | Improvements in or relating to organic compounds |
| US6555690B2 (en) * | 1996-06-21 | 2003-04-29 | Allergan, Inc. | Alkyl or aryl substituted dihydronaphthalene derivatives having retinoid and/or retinoid antagonist-like biological activity |
| US6346536B1 (en) | 1997-09-03 | 2002-02-12 | Guilford Pharmaceuticals Inc. | Poly(ADP-ribose) polymerase inhibitors and method for treating neural or cardiovascular tissue damage using the same |
| US6174913B1 (en) | 1998-06-05 | 2001-01-16 | The University Of North Carolina At Chapel Hill | Naphtho- and dihydrobenzo-thiophene derivatives as cytotoxic antitumor agents |
| TW200808810A (en) * | 2006-02-23 | 2008-02-16 | Novartis Ag | Organic compounds |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1089483A (en) * | 1964-02-04 | 1967-11-01 | Sandoz Ltd | Improvements in or relating to 4h-benzo(4,5)cyclohepta (1,2-b) thiophene derivatives |
| FR2138257B1 (enrdf_load_stackoverflow) * | 1971-05-21 | 1974-08-23 | Roussel Uclaf | |
| US4137323A (en) * | 1973-10-10 | 1979-01-30 | Sandoz Ltd. | Organic compounds |
| US4128549A (en) * | 1976-02-27 | 1978-12-05 | Sandoz Ltd. | Precursors of 4-(1-alkyl-4-piperidylidene-4H-benzo[4,5]cyclohepta-[1,2-b]thiophen-10(9H)-ones |
| US4267192A (en) * | 1980-03-11 | 1981-05-12 | American Home Products Corporation | Method for treating inflammation |
| US4282233B1 (en) * | 1980-06-19 | 2000-09-05 | Schering Corp | Antihistaminic 11-(4-piperidylidene)-5h-benzoÄ5,6Ü-cyclohepta-Ä1,2Ü-pyridines |
| AU2258683A (en) * | 1983-01-03 | 1984-07-05 | American Home Products Corporation | Dibenzocycloheptenylidenes and derivatives theof |
-
1984
- 1984-09-28 HU HU843690A patent/HU195800B/hu not_active IP Right Cessation
- 1984-10-01 EP EP84810475A patent/EP0138765B1/en not_active Expired
- 1984-10-01 AT AT84810475T patent/ATE45577T1/de not_active IP Right Cessation
- 1984-10-01 DE DE8484810475T patent/DE3479422D1/de not_active Expired
- 1984-10-10 PH PH31323A patent/PH23759A/en unknown
- 1984-10-10 IL IL73220A patent/IL73220A/xx unknown
- 1984-10-11 ES ES536737A patent/ES8606329A1/es not_active Expired
- 1984-10-11 CA CA000465206A patent/CA1242208A/en not_active Expired
- 1984-10-11 GR GR80607A patent/GR80607B/el unknown
- 1984-10-11 DK DK487884A patent/DK159110C/da not_active IP Right Cessation
- 1984-10-11 NZ NZ209848A patent/NZ209848A/en unknown
- 1984-10-11 AU AU34145/84A patent/AU574105B2/en not_active Ceased
- 1984-10-11 PT PT79344A patent/PT79344B/pt not_active IP Right Cessation
- 1984-10-11 FI FI843999A patent/FI81346C/fi not_active IP Right Cessation
- 1984-10-12 JP JP59215073A patent/JPS60104084A/ja active Granted
- 1984-10-12 ZA ZA847999A patent/ZA847999B/xx unknown
-
1987
- 1987-07-14 US US07/072,807 patent/US4740518A/en not_active Expired - Fee Related
- 1987-09-28 MY MYPI87002008A patent/MY102060A/en unknown
Non-Patent Citations (2)
| Title |
|---|
| Acta Cryst 37, pp. 279-281 (1981) * |
| Hel v. Chim Acta pp 866-877, vol. 59th August 198 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE45577T1 (de) | 1989-09-15 |
| PH23759A (en) | 1989-11-03 |
| DK487884A (da) | 1985-04-14 |
| DK159110C (da) | 1991-02-11 |
| EP0138765A2 (en) | 1985-04-24 |
| FI81346C (fi) | 1990-10-10 |
| CA1242208A (en) | 1988-09-20 |
| DE3479422D1 (en) | 1989-09-21 |
| JPH0246035B2 (enrdf_load_stackoverflow) | 1990-10-12 |
| IL73220A (en) | 1988-07-31 |
| FI81346B (fi) | 1990-06-29 |
| FI843999L (fi) | 1985-04-14 |
| PT79344A (en) | 1984-11-01 |
| DK159110B (da) | 1990-09-03 |
| GR80607B (en) | 1985-02-07 |
| AU574105B2 (en) | 1988-06-30 |
| US4740518A (en) | 1988-04-26 |
| HUT37779A (en) | 1986-02-28 |
| IL73220A0 (en) | 1985-01-31 |
| NZ209848A (en) | 1988-02-29 |
| JPS60104084A (ja) | 1985-06-08 |
| DK487884D0 (da) | 1984-10-11 |
| PT79344B (en) | 1986-09-08 |
| ZA847999B (en) | 1986-05-28 |
| HU195800B (en) | 1988-07-28 |
| MY102060A (en) | 1992-03-31 |
| ES8606329A1 (es) | 1986-04-16 |
| AU3414584A (en) | 1985-04-18 |
| ES536737A0 (es) | 1986-04-16 |
| FI843999A0 (fi) | 1984-10-11 |
| EP0138765A3 (en) | 1986-12-30 |
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